PROJECT SUMMARY This K24 proposal builds on over a decade of clinical and translational research ? which the candidate ? Dr. Tracy Manuck, MD, MSc, has focused on spontaneous preterm birth (SPTB). In this application, Dr. Manuck has recruited a team of multidisciplinary faculty experts to collaborate and support her in this endeavor, one that reflects the breadth and depth of UNC?s resources in environmental research. This work will greatly augment her current portfolio in patient-oriented research, allowing her to expand her current work and incorporate environmental contaminants into her current R01 funded study (R01-MD011609), creating a rich, multi- dimensional dataset. Candidate: Dr. Manuck is a recognized thought leader in the pharmacogenomics of SPTB. She has won numerous national accolades and has led high-impact clinical prematurity studies; here, she seeks to complement these skills by incorporating toxicogenomics into her research. Mentoring Plan/Environment: Dr. Manuck has an established track record in research training, including serving as Maternal Fetal Medicine (MFM) fellowship research director and a small group instructor for 2 graduate-level grant writing courses for fellows and junior faculty. However, competing administrative and clinical responsibilities limit her available time for mentorship. K24 award support will enable a more comprehensive mentoring portfolio within prematurity, and help to develop the critical mass of researchers investigating reproductive health effects of environmental contaminant exposure that is urgently needed in this field. With K24 support, she will have the appropriate time and resources to mentor advanced trainees (e.g., postdoctoral fellows, junior faculty) in their pursuit of independent funding. Dr. Manuck will leverage UNC?s extensive resources to accomplish this goal, including NIH-funded centers and training programs, networks and collaborations, and global health institutes. Career Goals and Objectives: Dr. Manuck will accomplish the following career development aims, including: Career Aim 1 - Expand knowledge of environmental health; Career Aim 2 - Improve mentorship skills; Career Aim 3 - Strengthen the ability to disseminate scientific results. Research Plan: Dr. Manuck will leverage her R01 study (currently recruiting) to evaluate the effects of exposure to pro-inflammatory environmental contaminants as an additional key driver of SPTB. She will integrate mentorship across the research aims: Aim 1 ? Quantify exposure to environmental contaminants during pregnancy through self-report and biomonitoring of maternal urine, serum, and placentas; Aim 2 ? Determine which contaminant or combination of contaminants is most strongly associated with SPTB; and Aim 3 ? Test the effects of gene x environment interactions on recurrent SPTB risk. This plan offers a framework for Dr. Manuck?s training in the incorporation of environmental contaminants into prematurity studies, with potential for lifelong impact on the >450,000 babies delivered too soon in the US each year, while simultaneously providing a platform for mentoring future investigators committed to patient-oriented research.